The effect of decontamination procedures on the pharmacodynamics of venlafaxine in overdose

Venkata V Pavan Kumar, Geoffrey K. Isbister, Stephen B Duffull

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14 Citations (Scopus)

Abstract

AIMS To investigate the relationship between decontamination procedures and seizure events caused by venlafaxine overdose and to estimate the time at which 90% of patients would have had their first seizure in the presence and absence of decontamination. METHODS Data were collected from 319 patients who took an overdose of venlafaxine on 436 occasions. Seizures occurred on 24 of 436 occasions (5%). Patients received one of single dose activated charcoal (SDAC), whole bowel irrigation (WBI), a combination of either (SDAC/WBI) or no decontamination. Logistic regression and time to event analysis were used to investigate the influence of dose and decontamination on the probability of seizures and time to 90% (t 90) of seizure, respectively. RESULTS A linear logistic regression model described the data. Simulation from the model showed that the probability of seizure was 0.05 (0.03-0.08), 0.19 (0.09-0.35) and 0.75 (0.30-0.96) at 1000, 5000 and 10000mg, respectively (median and 95% credible interval). At the mean dose of 2100mg the odds ratios (OR) in the presence of SDAC, WBI and SDAC/WBI were 0.48 (0.25-0.89), 0.71 (0.35-1.22) and 0.25 (0.08-0.62), respectively. A modified Gompertz model described the time to seizure events. Simulations from the Gompertz model showed that the t 90 values for first seizure was 26h and was not affected by dose or decontamination procedure. CONCLUSION SDAC/WBI provided greater benefits than the sum of the independent effects of SDAC and WBI. Patients should be observed for at least 24h for seizures based on the dose and risk of seizure occurring.

Original languageEnglish
Pages (from-to)125-132
Number of pages8
JournalBritish Journal of Clinical Pharmacology
Volume72
Issue number1
DOIs
Publication statusPublished - Jul 2011
Externally publishedYes

Keywords

  • Bayesian analysis
  • Overdose
  • Pharmacodynamics
  • Venlafaxine

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